Title:
造影剤の薬学的製剤を調製する方法
Document Type and Number:
Japanese Patent JP5469615
Kind Code:
B2
Abstract:
The present invention relates to a process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and a mol/mol amount of free macrocyclic chelate of between 0.002% and 0.4%, said macrocyclic chelate being DOTA and said lanthanide being gadolinium, said process comprising the following successive steps:b) preparing a liquid pharmaceutical composition containing:- the complex of macrocyclic chelate with a lanthanide,- free macrocyclic chelate that is not under the form of an excipient X[X',L] in which L is the macrocyclic chelate and X and X' are a metal ion, in particular chosen independently from calcium, sodium, zinc and magnesium, and/or- free lanthanide,by mixing a solution of free macrocyclic chelate and of free lanthanide so as to obtain complexation of the lanthanide by the macrocyclic chelate, wherein there is a difference between the amounts of free macrocyclic chelate and of free lanthanide added and the stoichiometric proportions;c) measuring, in the pharmaceutical formulation obtained in step b), the concentration of free macrocyclic chelate Cch land/or free lanthanide Clan l;d) adjusting, in the pharmaceutical formulation obtained in step b), Cch land Clan lso as to obtain Clan l= 0 and to obtain Cch l= Ct ch l, wherein Ct ch lis the target concentration of the free macrocyclic chelate in the final liquid pharmaceutical formulation and is selected in the range of between 0.002 % and 0.4 % mol/mol,said adjustment of Cch land of Clan lbeing performed as a function of the Clan land Cch lmeasured in step c),wherein the amount of free macrocyclic chelate in the final liquid pharmaceutical formulation corresponds to the proportion of free macrocyclic chelate relative to the amount of complexed macrocyclic chelate DOTA-Gd in the final liquid pharmaceutical formulation in mol/mol.
Inventors:
Mayer Dominique
Coro claire
Port mark
Barbotin Vincent
Bonne Main Bruno
Coro claire
Port mark
Barbotin Vincent
Bonne Main Bruno
Application Number:
JP2010547173A
Publication Date:
April 16, 2014
Filing Date:
February 18, 2009
Export Citation:
Assignee:
GUERBET
International Classes:
A61K49/00
Domestic Patent References:
| JP7505886A |
Other References:
Journal of Feline Medicine & Surgery,2007,Vol.9,No.4,340-345
Attorney, Agent or Firm:
Hatsushi Shimizu
Masao Haruna
Hirotaka Yamaguchi
Toshi Gobe
Ryuichi Inoue
Toshimitsu Sato
Koichi Niimi
Tomohiko Kobayashi
Shinichi Watanabe
Masato Ozeki
Yoshihiro Igarashi
Kazuya Kawamoto
Masao Haruna
Hirotaka Yamaguchi
Toshi Gobe
Ryuichi Inoue
Toshimitsu Sato
Koichi Niimi
Tomohiko Kobayashi
Shinichi Watanabe
Masato Ozeki
Yoshihiro Igarashi
Kazuya Kawamoto